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肾上腺皮质激素在脊髓中的作用:糖皮质激素受体的一些独特分子特性。

Adrenocorticoid action in the spinal cord: some unique molecular properties of glucocorticoid receptors.

作者信息

De Nicola A F, Moses D F, González S, Ortí E

机构信息

Laboratorio de Bioquímica Neuroendócrina, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.

出版信息

Cell Mol Neurobiol. 1989 Jun;9(2):179-92. doi: 10.1007/BF00713027.

Abstract
  1. Glucocorticoid hormones affect several functions of the spinal cord, such as synaptic transmission, biogenic amine content, lipid metabolism, and the activity of some enzymes (ornithine decarboxylase, glycerolphosphate dehydrogenase), indicating that this tissue is a target of adrenal hormones. 2. Corticosterone, the main glucocorticoid of the rat, is detected at all regional levels of the spinal cord, and cold stress increases this steroid, predominantly in the cervical regions. 3. Intracellular glucocorticoid receptors have been found in the spinal cord, with higher concentrations in the cervical and lumbar enlargements. Prima facie, these receptors presented biochemical, stereospecifical, and physicochemical properties similar to those of receptors found in other regions of the nervous system. The prevalent form in the spinal cord is the type II receptor, although type I is also present in small amounts. 4. The type II glucocorticoid receptor of the spinal cord shows an affinity lower (Kd 3.5 nM) than that of the hippocampal type II site (Kd 0.7 nM) when incubated with [3H]dexamethasone. This condition may impair the nuclear translocation of the spinal cord receptor. 5. Another peculiar property of spinal cord type II site is a greater affinity for DNA-cellulose binding than the hippocampal receptor during heat-induced transformation. Also, the spinal cord receptor shows resistance to the action of RNAse A, an enzyme which increases DNA-cellulose binding of the hippocampal receptor, indicating that both receptors may be structurally different. 6. Therefore, it is possible that a different subclass of type II, or "classical glucocorticoid receptor," is present in the spinal cord. This possibility makes the cord a useful system for studying diversity of glucocorticoid receptors of the nervous system, especially the relationship between receptor structure and function.
摘要
  1. 糖皮质激素会影响脊髓的多种功能,如突触传递、生物胺含量、脂质代谢以及某些酶(鸟氨酸脱羧酶、甘油磷酸脱氢酶)的活性,这表明该组织是肾上腺激素的作用靶点。2. 大鼠的主要糖皮质激素皮质酮在脊髓的所有区域水平均可检测到,冷应激会增加这种类固醇,主要是在颈部区域。3. 在脊髓中已发现细胞内糖皮质激素受体,在颈膨大及腰膨大处浓度更高。乍一看,这些受体呈现出与神经系统其他区域发现的受体相似的生化、立体特异性和物理化学特性。脊髓中普遍存在的形式是Ⅱ型受体,不过Ⅰ型也有少量存在。4. 当与[³H]地塞米松孵育时,脊髓的Ⅱ型糖皮质激素受体显示出比海马体Ⅱ型位点(解离常数Kd为0.7 nM)更低的亲和力(Kd为3.5 nM)。这种情况可能会损害脊髓受体的核转位。5. 脊髓Ⅱ型位点的另一个独特特性是,在热诱导转化过程中,它对DNA纤维素结合的亲和力比海马体受体更高。此外,脊髓受体对核糖核酸酶A的作用具有抗性,核糖核酸酶A会增加海马体受体与DNA纤维素的结合,这表明这两种受体在结构上可能不同。6. 因此,脊髓中可能存在不同亚类的Ⅱ型,即“经典糖皮质激素受体”。这种可能性使得脊髓成为研究神经系统糖皮质激素受体多样性,特别是受体结构与功能之间关系的有用系统。

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